Computational Cross-Aggregation Study of Dengue Virus NS1, Capsid Anchor and 2k Peptides With Human Amylin, Aβ42 and...

Dengue virus, an arbovirus, is the causal factor of thousands of deaths around the globe, although the long-term consequences of the same have not been elucidated in great detail. The virus encodes for a polyprotein, which is later cleaved to form multiple proteins, of which NS1 protein oligomerization domain, 2k, and capsid anchor are three aggregation-prone peptides, as have been previously seen. A relatively under-studied angle of these peptides is the role of these peptides in cross-aggregation with certain human aggregation-prone proteins. Here, we have tried to shed light on this cross-aggregation perspective of these three peptides in combination with human amylin, α-synuclein, and Aβ42 peptides, making use of extensive all-atom MD simulations to study the cross-aggregation behavior of the peptides in atomistic detail. The intricacies of peptide aggregation have been studied based on the aggregate size calculation and the solvent accessible surface area method, giving a direct estimate of the aggregation seed development process. The importance of the different peptide residues in both self and cross-aggregation has been elucidated. This study may shed light on the cross-aggregation potential of these three peptides and help to explain the viral pathogenesis pathway in greater detail.